In vivo insulin action and resistance. The hyperinsulinaemic, euglycaemic clamp technique in conscious rats

Abstract

• After almost 75 years of research and four Nobel prizes awarded for insulin-related investigations, we still do not understand how insulin works. Of course, substantial progress has been made and there are some clues. We review in vivo insulin action from the moment of insulin biosynthesis in the pancreatic fi-cell to insulin action on effector systems in target tissues. The mechanism of insulin action at the whole body, tissue and cellular level is discussed. In addition, factors and conditions influencing insulin action and events leading to insulin resistance are summarized. Finally, the reader is introduced into the principles of the hyperinsulinaemic, euglycaemic clamp technique which is considered the "golden standard" for measurement of insulin action and resistance in vivo. An example is given how to clamp conscious rats in a proper way.